RESUMEN
Previous studies have observed evoked response latency as well as gamma band superior temporal gyrus (STG) auditory abnormalities in individuals with autism spectrum disorders (ASD). A limitation of these studies is that associations between these two abnormalities, as well as the full extent of oscillatory phenomena in ASD in terms of frequency and time, have not been examined. Subjects were presented pure tones at 200, 300, 500, and 1,000 Hz while magnetoencephalography assessed activity in STG auditory areas in a sample of 105 children with ASD and 36 typically developing controls (TD). Findings revealed a profile such that auditory STG processes in ASD were characterized by pre-stimulus abnormalities across multiple frequencies, then early high-frequency abnormalities followed by low-frequency abnormalities. Increased pre-stimulus activity was a 'core' abnormality, with pre-stimulus activity predicting post-stimulus neural abnormalities, group membership, and clinical symptoms (CELF-4 Core Language Index). Deficits in synaptic integration in the auditory cortex are associated with oscillatory abnormalities in ASD as well as patient symptoms. Increased pre-stimulus activity in ASD likely demonstrates a fundamental signal-to-noise deficit in individuals with ASD, with elevations in oscillatory activity suggesting an inability to maintain an appropriate 'neural tone' and an inability to rapidly return to a resting state prior to the next stimulus.
Asunto(s)
Corteza Auditiva/fisiopatología , Ondas Encefálicas/fisiología , Trastornos Generalizados del Desarrollo Infantil/fisiopatología , Trastornos Generalizados del Desarrollo Infantil/psicología , Potenciales Evocados Auditivos/fisiología , Trastornos del Desarrollo del Lenguaje/fisiopatología , Estimulación Acústica , Adolescente , Estudios de Casos y Controles , Niño , Trastornos Generalizados del Desarrollo Infantil/complicaciones , Femenino , Humanos , Lenguaje , Magnetoencefalografía , Masculino , Tiempo de Reacción/fisiologíaRESUMEN
BACKGROUND: The development of left and right superior temporal gyrus (STG) 50 ms (M50) and 100 ms (M100) auditory responses in typically developing (TD) children and in children with autism spectrum disorder (ASD) was examined. Reflecting differential development of primary/secondary auditory areas and supporting previous studies, it was hypothesized that whereas left and right M50 STG responses would be observed equally often in younger and older children, left and right M100 STG responses would more often be absent in younger than older children. In ASD, delayed neurodevelopment would be indicated via the observation of a greater proportion of ASD than TD subjects showing missing M100 but not M50 responses in both age groups. Missing M100 responses would be observed primarily in children with ASD with language impairment (ASD + LI) (and perhaps concomitantly lower general cognitive abilities). METHODS: Thirty-five TD controls, 63 ASD without language impairment (ASD - LI), and 38 ASD + LI were recruited. Binaural tones were presented. The presence or absence of a STG M50 and M100 was scored. Subjects were grouped into younger (6-10 years old) and older groups (11-15 years old). RESULTS: Although M50 responses were observed equally often in older and younger subjects and equally often in TD and ASD, left and right M50 responses were delayed in ASD - LI and ASD + LI. Group comparisons showed that in younger subjects M100 responses were observed more often in TD than ASD + LI (90 versus 66%, p = 0.04), with no differences between TD and ASD - LI (90 versus 76%, p = 0.14) or between ASD - LI and ASD + LI (76 versus 66%, p = 0.53). In older subjects, whereas no differences were observed between TD and ASD + LI, responses were observed more often in ASD - LI than ASD + LI. Findings were similar when splitting the ASD group into lower- and higher-cognitive functioning groups. CONCLUSION: Although present in all groups, M50 responses were delayed in ASD. Examining the TD data, findings indicated that by 11 years, a right M100 should be observed in 100% of subjects and a left M100 in 80% of subjects. Thus, by 11 years, lack of a left and especially right M100 offers neurobiological insight into sensory processing that may underlie language or cognitive impairment.
RESUMEN
BACKGROUND: Auditory processing abnormalities are frequently observed in autism spectrum disorders (ASD), and these abnormalities may have sequelae in terms of clinical language impairment (LI). The present study assessed associations between language impairment and the amplitude and latency of the superior temporal gyrus magnetic mismatch field (MMF) in response to changes in an auditory stream of tones or vowels. METHODS: Fifty-one children with ASD, and 27 neurotypical control subjects, all aged 6 to 15 years, underwent neuropsychological evaluation, including tests of language function, as well as magnetoencephalographic recording during presentation of tones and vowels. The MMF was identified in the difference waveform obtained from subtraction of responses to standard from deviant stimuli. RESULTS: Magnetic mismatch field latency was significantly prolonged (p < .001) in children with ASD, compared with neurotypical control subjects. Furthermore, this delay was most pronounced (â¼50 msec) in children with concomitant LI, with significant differences in latency between children with ASD with LI and those without (p < .01). Receiver operator characteristic analysis indicated a sensitivity of 82.4% and specificity of 71.2% for diagnosing LI based on MMF latency. CONCLUSIONS: Neural correlates of auditory change detection (the MMF) are significantly delayed in children with ASD, and especially those with concomitant LI, suggesting a neurobiological basis as well as a clinical biomarker for LI in ASD.
Asunto(s)
Corteza Auditiva/fisiopatología , Trastorno Autístico/complicaciones , Potenciales Evocados Auditivos/fisiología , Trastornos del Lenguaje/diagnóstico , Estimulación Acústica , Adolescente , Trastorno Autístico/fisiopatología , Niño , Femenino , Humanos , Trastornos del Lenguaje/complicaciones , Trastornos del Lenguaje/fisiopatología , Pruebas del Lenguaje , Magnetoencefalografía , Masculino , Pruebas Neuropsicológicas , Tiempo de Reacción/fisiologíaRESUMEN
Motivated by auditory and speech deficits in autism spectrum disorders (ASD), the frequency dependence of superior temporal gyrus (STG) 50 msec (M50) and 100 msec (M100) neuromagnetic auditory evoked field responses in children with ASD and typically developing controls were evaluated. Whole-cortex magnetoencephalography (MEG) was obtained from 17 typically developing children and 25 children with ASD. Subjects were presented tones with frequencies of 200, 300, 500, and 1,000 Hz, and left and right STG M50 and M100 STG activity was examined. No M50 latency or amplitude Group differences were observed. In the right hemisphere, a Group x Frequency ANOVA on M100 latency produced a main effect for Group (P=0.01), with an average M100 latency delay of 11 msec in children with ASD. In addition, only in the control group was the expected association of earlier M100 latencies in older than younger children observed. Group latency differences remained significant when hierarchical regression analyses partialed out M100 variance associated with age, IQ, and language ability (all P-values <0.05). Examining the right-hemisphere 500 Hz condition (where the largest latency differences were observed), a sensitivity of 75%, a specificity of 81%, and a positive predictive value (PPV) of 86% was obtained at a threshold of 116 msec. The M100 latency delay indicates disruption of encoding simple sensory information. Given similar findings in language impaired and non-language impaired ASD subjects, a right-hemisphere M100 latency delay appears to be an electrophysiological endophenotype for autism.
Asunto(s)
Biomarcadores , Trastornos Generalizados del Desarrollo Infantil/diagnóstico , Trastornos Generalizados del Desarrollo Infantil/fisiopatología , Potenciales Evocados Auditivos/fisiología , Magnetoencefalografía , Tiempo de Reacción/fisiología , Procesamiento de Señales Asistido por Computador , Estimulación Acústica , Factores de Edad , Artefactos , Corteza Auditiva/fisiopatología , Mapeo Encefálico , Niño , Dominancia Cerebral/fisiología , Electroencefalografía , Electrooculografía , Femenino , Humanos , Inteligencia/fisiología , Trastornos del Desarrollo del Lenguaje/diagnóstico , Trastornos del Desarrollo del Lenguaje/fisiopatología , Masculino , Valores de ReferenciaRESUMEN
White matter diffusion anisotropy in the acoustic radiations of the auditory pathway was characterized as a function of development in children and adolescents. Auditory-evoked neuromagnetic fields were also recorded from the same individuals, and the latency of the left and right superior temporal gyrus auditory response of approximately 100 ms was also obtained. White matter diffusion anisotropy increased with age. There was a commensurate shortening of the auditory-evoked response latency with increased age as well as with increased white matter diffusion anisotropy. The significant negative correlation between structural integrity of white matter pathways and electrophysiological function (response timing) of distal cortex supports a biophysical model of developmental changes in white matter myelination, conduction velocity, and cortical response timing.